Alendronate and naproxen are synergistic for development of gastric ulcers

Arch Intern Med. 2001 Jan 8;161(1):107-10. doi: 10.1001/archinte.161.1.107.


Background: Both alendronate sodium use and nonsteroidal anti-inflammatory drug use are associated with gastric ulcers. The aim of this study was to investigate whether alendronate and naproxen are synergistic as causes of gastric ulcers.

Methods: We performed an endoscopist-blind, randomized, crossover, single-center comparison of 10 mg/d of alendronate sodium, 500 mg of naproxen sodium twice daily, or the combination taken orally for 10 days in volunteers aged 30 years or older. Videoendoscopy was used to evaluate the presence and degree of mucosal damage to the esophagus, stomach, or duodenal bulb before and after each treatment. There was a 1- to 4-week washout between evaluations.

Results: Twenty-six healthy volunteers participated (18 women and 8 men), aged 30 to 50 years. Gastric ulcers were present in 2 subjects receiving alendronate (8%), in 3 receiving naproxen (12%), and in 10 receiving both (38%) (P<.05 for the combination vs either drug alone).

Conclusions: Both alendronate and naproxen can cause gastric ulcers. The combination appears synergistic. Alendronate should be used with caution in those who simultaneously require nonsteroidal anti-inflammatory drugs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alendronate / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cross-Over Studies
  • Drug Synergism
  • Duodenal Ulcer / chemically induced
  • Female
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Gastroscopy
  • Humans
  • Male
  • Middle Aged
  • Naproxen / adverse effects*
  • Single-Blind Method
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Naproxen
  • Alendronate